6-O-methylerythromycin A (Clarithromycin) is a semisynthetic macrolide antibiotic of formula ##STR1## Two distinct crystal forms of 6-O-methylerythromycin A, designated "form I" and "form II" have been identified. The crystal forms are identified by their single crystal or powder diffraction patterns.
6-O-methylerythromycin A exhibits excellent antibacterial activity against gram-positive bacteria, some gram-negative bacteria, anaerobic bacteria, Mycoplasma, and Chlamidia. It is stable under acidic conditions and is efficacious when administered orally. It is a useful therapy for infections of the upper respiratory tract in children and adults. 6-O-methylerythromycin A is available as tablets and as an oral suspension. Drugs currently on the market are formulated using the thermodynamically more stable 6-O-methylerythromycin A form II.
The oral suspension is particularly useful for patients such as children and the elderly who have difficulty swallowing the tablets. However, because 6-O-methylerythromycin A has such pronounced bitterness conventional approaches to taste masking failed to produce palatable suspensions. Ultimately, it was discovered that 6-O-methylerythromycin A-carbomer (acrylic acid copolymer) complexes provided particles sufficiently palatable for use in the oral suspension. See U.S. Pat. No. 4,808,411.
The 6-O-methylerythromycin A-carbomer complexes used in the oral suspension are prepared by dispersing 6-O-methylerythromycin A in an organic solvent, preferably ethanol, separately dispersing the carbomer in ethanol, mixing the two solutions to allow formation of the desired reaction product, evaporating most of the solvent and diluting the mixture with water to precipitate the carbomer6-O-methylerythromycin A form 0 solvate complex.